Box 1 - Treatment allocation. What’s so special about randomisation?

The method used to assign interventions to trial participants is a crucial aspect of clinical trial design. Random assignment is the preferred method; it has been successfully used regularly in trials for more than 50 years.(24) Randomisation has three major advantages.(25) First, when properly implemented, it eliminates selection bias, balancing both known and unknown prognostic factors, in the assignment of treatments. Without randomisation, treatment comparisons may be prejudiced, whether consciously or not, by selection of participants of a particular kind to receive a particular treatment. Second, random assignment permits the use of probability theory to express the likelihood that any difference in outcome between intervention groups merely reflects chance.(26) Third, random allocation, in some situations, facilitates blinding the identity of treatments to the investigators, participants, and evaluators, possibly by use of a placebo, which reduces bias after assignment of treatments.(27) Of these three advantages, reducing selection bias at trial entry is usually the most important.(28)

Successful randomisation in practice depends on two interrelated aspects—adequate generation of an unpredictable allocation sequence and concealment of that sequence until assignment occurs.(2) (23) A key issue is whether the schedule is known or predictable by the people involved in allocating participants to the comparison groups.(29) The treatment allocation system should thus be set up so that the person enrolling participants does not know in advance which treatment the next person will get, a process termed allocation concealment.(2) (23) Proper allocation concealment shields knowledge of forthcoming assignments, whereas proper random sequences prevent correct anticipation of future assignments based on knowledge of past assignments.

Page last edited: 24 March 2010